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[Acute hepatitis in heroin addicts: etiologic and follow-up study of 110 cases].

In order to know the etiology and natural history of acute viral hepatitis in intravenous drugs abusers, a panel of 110 heroin addicts, suffering acute hepatitis, is studied. The B virus, by itself or in conjunction with the delta virus was responsible for 63 cases. 35 patients suffered of NANB hepatitis and only two patients were diagnosed of hepatitis A. Delta infection was detected in 38 of the 77 cases of HBsAg-positive acute hepatitis. All the hepatitis B patients had serum conversion within the first 6 months of the acute episode. All the patients suffering acute delta hepatitis and 75% of those suffering non-A, non-B hepatitis, developed chronic hepatic disease. We conclude that in our environment, the B virus is the main responsible for acute hepatitis in heroin addicts. Delta infection is detected in almost half of the heroin addicts with HBsAg-positive acute hepatitis. The acute hepatitis caused by B virus, or by B and delta viruses simultaneously, have a satisfactory evolution, thus, almost all the cases are cured within 6 months. On the contrary, hepatitis caused by NANB or delta viruses usually progresses to chronic hepatic disease.

Adolescent↗

[Assessment of the epidemiological parameters of the most widespread viral diseases in the Socialist Republic of Romania and in Sibiu County for period 1967-1986].

Essential peculiarities of the kinetics of the morbidity evolution of most frequent virus diseases were explained using a determinant mathematical model. The main epidemiological parameters for the whole territory of the S.R. of Romania and of Sibiu County were evaluated for the 1967-1986 period.

Epidemiologic Methods↗

[Evaluation of liver biopsies in chronic hepatitis].

New knowledge of the different hepatitis viruses and of the evolution of chronic viral hepatitis has necessitated review of the nomenclature of chronic hepatitis and of its histological categories. Some hepatologists now prefer to use a primarily aetiological classification, supplemented by histological data. The latter may be expressed in semiquantitative terms, which helps in the assessment of new therapies.

Biopsy↗

[Evolution of the emergency consultations in patients with human immunodeficiency virus infection in various levels of medical care in an urban area of Barcelona].

Medical emergencies involving patients with Human Immunodeficiency Virus (HIV) infection comprise an increasing number of the total hospitalary consults and contribute to their overflow. In order to evaluate possible alternative solutions to this problem, we performed a retrospective study of urgent medical consults by HIV patients at three different levels of medical care (primary assistance, extrahospitalary and hospitalary emergencies centers) all included in the same urban area of Barcelona. We demonstrated a growing excess in hospitalary emergencies, with high requirements of complementary explorations and hospitalary admittances. In the extrahospitalary emergency center, we can observe a progressive increasing of emergency consults, but still reasonable in number and adequate to the real possibilities of the center. At primary care level, HIV patients consulted because of less severe reasons. We conclude that a possible solution in order to decrease the assistance requirements in the hospitalary emergencies level could be to try to attend these patients in emergency extrahospitalary centers. These centers should be technically provided and with a close relationship both with the primary assistance care level and with the reference hospital.

Adult↗

Evolution of a disrupted TAR RNA hairpin structure in the HIV-1 virus.

Human immunodeficiency virus type 1 (HIV-1) RNA contains an extended hairpin structure at the 5' end (the TAR element) that is essential for viral replication. The upper part of the stem-loop structure binds the virally encoded transcriptional activator protein Tat and cellular co-factors, but no clear function for the lower stem region has been established. Here, we report that mutant HIV-1 viruses with base substitutions in the lower stem region are dead, most likely at the level of transcription from an integrated provirus. By using large amounts of these mutant DNA constructs for transfections, revertant viruses with a great variety of genetic changes (point mutations, short deletions) could be isolated in prolonged culture experiments that lasted over 6 months. The pattern and evolution of these changes supported the notion that base-pairing of the lower stem region is essential for optimal HIV-1 replication. The functional and genetic plasticities of this RNA domain and the HIV-1 long terminal repeat promoter are discussed.

Base Composition↗

[Effect of methadone or naltrexone on the course of transaminases in parenteral drug users with hepatitis C virus infection].

A prospective study was conducted on the evolution of serum transaminases in 116 patients infected with hepatitis C virus (HCV), parenteral drug abusers, included for 6 months in treatment programs with methadone, naltrexone or "drug free" regimen. Treatment with methadone or naltrexone did not result in a transaminase increase in these patients. In contrast, patients included in the drug-free program appear to have a higher increase in serum transaminase levels than those treated with methadone or naltrexone (146.1 +/- 122.29 vs 91.88 +/- 81.96 and 86.99 +/- 64.26 Ul/ml, respectively). Such an increase originated mainly from patients who anytime during follow-up had a liver necrosis outbreak in the acute hepatitis range, and is offset if, instead of a given transaminase value, we consider a simplified liver necrosis index (1.28 +/- 0.74 vs 0.95 +/- 0.72 and 1.01 +/- 0.65, respectively; p > 0.05). HIV infected patients have serum transaminase values similar to those in HIV-negative patients (80.61 +/- 58.81 vs 113.63 +/- 99.59, respectively; p > 0.05).

Adult↗

Evolution of envelope-specific antibody responses in monkeys experimentally infected or immunized with simian immunodeficiency virus and its association with the development of protective immunity.

Previous studies of attenuated simian immunodeficiency virus (SIV) vaccines in rhesus macaques have demonstrated the development of broad protection against experimental challenge, indicating the potential for the production of highly effective immune responses to SIV antigens. However, the development of this protective immune status was found to be critically dependent on the length of time postvaccination with the attenuated virus strain, suggesting a necessary maturation of immune responses. In this study, the evolution of SIV envelope-specific antibodies in monkeys experimentally infected with various attenuated strains of SIV was characterized by using a comprehensive panel of serological assays to assess the progression of antibodies in longitudinal serum samples that indicate the development of protective immunity. In parallel studies, we also used the same panel of antibody assays to characterize the properties of SIV envelope-specific antibodies elicited by inactivated whole-virus and envelope subunit vaccines previously reported to be ineffective in producing protective immunity. The results of these studies demonstrate that the evolution of protective immunity in monkeys inoculated with attenuated strains of SIV is associated with a complex and lengthy maturation of antibody responses over the first 6 to 8 months postinoculation, as reflected in progressive changes in antibody conformational dependence and avidity properties. The establishment of long-term protective immunity at this time in general parallels the absence of further detectable changes in antibody responses and a maintenance of relatively constant antibody titer, avidity, conformational dependence, and the presence of neutralizing antibody for at least 2 years postinoculation. In contrast to the mature antibody responses elicited by the attenuated SIV vaccines, the whole-virus and envelope subunit vaccines in general elicited only immature antibody responses characterized by poor reactivity with native envelope proteins, low avidity, low conformational dependence, and the absence of neutralization activity against the challenge strain. Thus, these studies establish for the first time an association between the effectiveness of experimental vaccines and the capacity of the vaccine to produce a mature antibody response to SIV envelope proteins and further indicate that a combination of several antibody parameters (including titer, avidity, conformational dependence, and virus neutralization) are superior to any single antibody parameter as prognostic indicators to evaluate candidate AIDS vaccines.

Animals↗

Evolutionary mechanisms of persistence and diversification of a calicivirus within endemically infected natural host populations.

In order to understand the evolutionary mechanisms of persistence and diversification within the Caliciviridae, we have been exploiting endemic infection of feline calicivirus within five geographically distinct household groups of cats. By sequencing immunodominant and variable regions of the capsid gene, we identified the relative contribution of the different evolutionary processes employed by the virus to ensure its long-term survival in the host population. Such strategies included progressive evolution of a given variant of a strain through mutation accumulation within an individual, sequential reinfection with either a variant of the same strain or with a different strain, and mixed infection. Recombination between different strains in this study has been reported in detail elsewhere (K. P. Coyne et al., J. Gen. Virol. 87:921-926, 2006). Here, we provide evidence to suggest that true long-term persistent infection in individuals is relatively rare, with the majority of apparent viral carriers undergoing a combination of progressive evolution and cyclical reinfection. Progressive evolution at the individual level and variant reinfection at both the individual and population levels were associated with positive selection. Two measures of evolution rate were determined; for a virus progressively evolving within an individual (1.32 x 10(-2) to 2.64 x 10(-2) substitutions per nucleotide per year, i.e., no transmission) and for a strain circulating within a population (3.84 x 10(-2) to 4.56 x 10(-2) substitutions per nucleotide per year, i.e., including transmission). Reiteration of both progressive evolution and variant reinfection appeared to lead to a gradual increase in the diversity of a given strain of virus, both in the individual and in the population, until eventually new strains emerged.

Animals↗

Genomic organization and evolution of the human herpesviruses.

Members of the Herpesviridae family have been isolated from most animal species examined. Of approximately 100 individual virus species, eight have been isolated from humans, and three of these only within the last 10 years. Fortunately, there is now an enormous amount of sequence data from many of these viruses, particularly the eight human herpesviruses. This wealth of sequence information from such a diverse group of related viruses provides a unique resource for studies of viral gene evolution, comparative gene function, and virus identification.

Evolution, Molecular↗

Conservation and host specificity of Vpr-mediated cell cycle arrest suggest a fundamental role in primate lentivirus evolution and biology.

The human immunodeficiency virus type 1 (HIV-1) Vpr protein prevents infected cells from passing through mitosis by arresting them in the G2 phase of the cell cycle. Vpr is conserved among all primate lentiviruses, suggesting an important role in the virus life cycle. Moreover, in this study we show that the ability to cause cell cycle arrest is also conserved in Vpr proteins from a wide variety of both tissue culture-passaged and uncultured human (HIV-1 and HIV-2), sooty mangabey (simian immunodeficiency virus SIV(SM)), African green monkey (SIV(AGM)), and Sykes' monkey (SIV(SYK)) isolates. However, this property is cell type specific and appears to depend on the particular primate species from which the cells are derived. SIV(AGM) and SIV(SYK) Vpr proteins are capable of arresting African green monkey cells but are completely inactive in human cells. By contrast, HIV-1, HIV-2, and SIV(SM) Vpr proteins function in both simian and human cell types, although SIV(SM) Vpr functions more efficiently in simian cells than it does in human cells. Neither differential protein stability nor subcellular localization explains the species-specific activities of these proteins. These results thus suggest that Vpr exerts its G2 arrest function by interacting with cellular factors that have evolved differently among the various primate species.

Animals↗

A novel simian immunodeficiency virus from black mangabey (Lophocebus aterrimus) in the Democratic Republic of Congo.

In order to understand primate lentivirus evolution, characterization of additional simian immunodeficiency virus (SIV) strains is essential. Here, an SIV from a black mangabey (Lophocebus aterrimus) originating from the Democratic Republic of Congo was analysed phylogenetically. The monkey had cross-reactive antibodies against human immunodeficiency virus type 1 (HIV-1) and HIV-2. The viral pol region sequence was amplified by nested PCR and sequence analysis confirmed that it was related to known SIV sequences. This is the first report to characterize genetically an SIV from the monkey genus Lophocebus. Phylogenetic analysis of the pol region revealed that this novel SIV, designated SIVbkm, fell into the SIVsyk and SIVgsn virus group, containing viruses isolated from the genus Cercopithecus, and suggests that cross-species transmission has occurred between species of the genera Lophocebus and Cercopithecus.

Animals↗

Lack of correlation between SIV-Nef evolution and rapid disease progression in morphine-dependent nonhuman primate model of AIDS.

Six morphine-dependent and two control macaques were infected in an SIV/SHIV nonhuman primate model of AIDS. Three animals in the morphine group rapidly developed clinical disease and died within the timeframe of this study. The sequence evolution of nef in plasma virus was assessed at 4, 12, and 20 weeks postinfection. Cloned sequences were compared phylogenetically against each other as well as against the inoculum virus clones to determine the effect of morphine and rate of disease progression on diversity and divergence, respectively. Unlike our earlier studies of tat and env, nef evolution was not affected by morphine abuse or by rapid disease progression. The results suggest that although the evolution of other loci is inversely correlated to the onset and rate of clinical disease, differential evolution of nef is related neither to drug abuse nor to rapid progression within the first 20 weeks of infection.

Animals↗

[Acute pancreatitis and infection with the human immunodeficiency virus].

BACKGROUND: Retrospective study of the etiology and evolution of 40 episodes of acute pancreatitis in 28 patients infected with the human immunodeficiency virus (HIV). RESULTS: AIDS criteria were met by 89.3% of patients. The likely etiology was an opportunist infection in 32.5% of episodes, drug use in 22.5%, and biliary lithiasis in 5%. AP secondary to AIDS-associated cholangitis occurred in 35.7% of episodes. Sixty percent of episodes were severe in nature. The mortality rate reached 30%. CONCLUSIONS: AP in HIV infected patients: a) is more frequent in the advanced stages of disease; b) opportunistic infections and drugs are the most frequent causes in our environment; c) in a third of patients it is probably secondary to AIDS associated cholangitis; d) biliary lithiasis seems to be less common than in the general population, and e) it is associated with a high severity and mortality.

AIDS-Related Opportunistic Infections↗

The effect of drug-injection behavior on genetic evolution of HIV-1.

The effect of injection-drug use on human immunodeficiency virus type 1 (HIV-1) env genetic evolution was examined in 15 seroconverting injection-drug users followed up for 4 years. After adjustment for non-drug-related independent variables significantly associated with genetic diversity (time since seroconversion and progressor status), injection frequency was positively and highly significantly associated with HIV-1 env genetic diversity (P=.003). The mutation rate in those who had injected at least once a day during the previous 6 months was estimated to be 62% greater than the rate in those who had not injected at all. If the positive effect of drug-injection frequency on env genetic diversity extends to the HIV-1 pol gene, the risk of emergence of resistance to antiretroviral drugs may be enhanced by increased drug-injection frequency, especially under the selection pressure of antiretroviral therapy.

Adult↗

Replication of single viruses across the kingdoms, Fungi, Plantae, and Animalia.

It is extremely rare that a single virus crosses host barriers across multiple kingdoms. Based on phylogenetic and paleovirological analyses, it has previously been hypothesized that single members of the family Partitiviridae could cross multiple kingdoms. Partitiviridae accommodates members characterized by their simple bisegmented double-stranded RNA genome; asymptomatic infections of host organisms; the absence of an extracellular route for entry in nature; and collectively broad host range. Herein, we show the replicability of single fungal partitiviruses in three kingdoms of host organisms: Fungi, Plantae, and Animalia. Betapartitiviruses of the phytopathogenic fungusRosellinia necatrix could replicate in protoplasts of the carrot (Daucus carota), Nicotiana benthamiana and Nicotiana tabacum, in some cases reaching a level detectable by agarose gel electrophoresis. Moreover, betapartitiviruses showed more robust replication than the tested alphapartitiviruses. One of the fungal betapartitiviruses, RnPV18, could persistently and stably infect carrot plants regenerated from virion-transfected protoplasts. Both alpha- and betapartitiviruses, although with different host preference, could replicate in two insect cell lines derived from the fall armyworm Spodoptera frugiperda and the fruit fly Drosophila melanogaster. Our results indicate the replicability of single partitiviruses in members of three kingdoms and provide insights into virus adaptation, host jumping, and evolution.

Animals↗